Maintenance of Lognormal-Like Skewed Dendritic Spine Size Distributions in Dentate Granule Cells of TNF, TNF-R1, TNF-R2, and TNF-R1/2-Deficient Mice.

Dendritic spines are sites of synaptic plasticity and their head size correlates with the strength of the corresponding synapse. We recently showed that the distribution of spine head sizes follows a lognormal-like distribution even after blockage of activity or plasticity induction. As the cytokine tumor necrosis factor (TNF) influences synaptic transmission and constitutive TNF and receptor (TNF-R)-deficiencies cause changes in spine head size distributions, we tested whether these genetic alterations disrupt the lognormality of spine head sizes.

Performance evaluation of iterative PET reconstruction with resolution recovery incorporating Gallium-68 positron range correction.

Background: The distance traveled by the positron before annihilation with an electron, the so-called positron range, negatively effects the positron emission tomography (PET) image quality for radionuclides emitting high-energy positrons such as Gallium-68 (Ga).

Purpose: In this study, the effect of a tissue-independent positron range correction for Gallium-68 (Ga-PRC) was investigated based on phantom measurements. The effect of the Ga-PRC was also explored in four patients.

Sex- and cycle-dependent changes in spine density and size in hippocampal CA2 neurons.

Sex hormones affect structural and functional plasticity in the rodent hippocampus. However, hormone levels not only differ between males and females, but also fluctuate across the female estrous cycle. While sex- and cycle-dependent differences in dendritic spine density and morphology have been found in the rodent CA1 region, but not in the CA3 or the dentate gyrus, comparable structural data on CA2, i.

Hypoxia induced deregulation of sphingolipids in colon cancer is a prognostic marker for patient outcome.

Sphingolipids are important for the physicochemical properties of cellular membranes and deregulated in tumors. In human colon cancer tissue ceramide synthase (CerS) 4 and CerS5 are reduced which correlates with a reduced survival probability of late-stage colon cancer patients. Both enzymes are reduced after hypoxia in advanced colorectal cancer (CRC) cells (HCT-116, SW620) but not in non-metastatic CRC cells (SW480, Caco-2).

Skewed distribution of spines is independent of presynaptic transmitter release and synaptic plasticity, and emerges early during adult neurogenesis.

Dendritic spines are crucial for excitatory synaptic transmission as the size of a spine head correlates with the strength of its synapse. The distribution of spine head sizes follows a lognormal-like distribution with more small spines than large ones. We analysed the impact of synaptic activity and plasticity on the spine size distribution in adult-born hippocampal granule cells from rats with induced homo- and heterosynaptic long-term plasticity and CA1 pyramidal cells from Munc13-1/Munc13-2 knockout mice with completely blocked synaptic transmission.

The Amyloid Precursor Protein Regulates Synaptic Transmission at Medial Perforant Path Synapses.

The perforant path provides the primary cortical excitatory input to the hippocampus. Because of its important role in information processing and coding, entorhinal projections to the dentate gyrus have been studied in considerable detail. Nevertheless, synaptic transmission between individual connected pairs of entorhinal stellate cells and dentate granule cells remains to be characterized.

Layer-specific changes of KCC2 and NKCC1 in the mouse dentate gyrus after entorhinal denervation.

The cation-chloride cotransporters KCC2 and NKCC1 regulate the intracellular Cl concentration and cell volume of neurons and/or glia. The Cl extruder KCC2 is expressed at higher levels than the Cl transporter NKCC1 in mature compared to immature neurons, accounting for the developmental shift from high to low Cl concentration and from depolarizing to hyperpolarizing currents through GABA-A receptors. Previous studies have shown that KCC2 expression is downregulated following central nervous system injury, returning neurons to a more excitable state, which can be pathological or adaptive.

Structural plasticity of the axon initial segment in rat hippocampal granule cells following high frequency stimulation and LTP induction.

The axon initial segment (AIS) is the site of action potential initiation and important for the integration of synaptic input. Length and localization of the AIS are dynamic, modulated by afferent activity and contribute to the homeostatic control of neuronal excitability. Synaptopodin is a plasticity-related protein expressed by the majority of telencephalic neurons.

Precise measurement of gene expression changes in mouse brain areas denervated by injury.

Quantitative PCR (qPCR) is a widely used method to study gene expression changes following brain injury. The accuracy of this method depends on the tissue harvested, the time course analyzed and, in particular on the choice of appropriate internal controls, i.e.

Loss of tumor necrosis factor (TNF)-receptor 1 and TNF-receptor 2 partially replicate effects of TNF deficiency on dendritic spines of granule cells in mouse dentate gyrus.

The cytokine tumor necrosis factor (TNF) is involved in the regulation of physiological and pathophysiological processes in the central nervous system. In previous work, we showed that mice lacking constitutive levels of TNF exhibit a reduction in spine density and changes in spine head size distribution of dentate granule cells. Here, we investigated which TNF-receptor pathway is responsible for this phenotype and analyzed granule cell spine morphology in TNF-R1-, TNF-R2-, and TNF-R1/R2-deficient mice.

BET and CDK Inhibition Reveal Differences in the Proliferation Control of Sympathetic Ganglion Neuroblasts and Adrenal Chromaffin Cells.

Neuroblastoma arising from the adrenal differ from ganglionic neuroblastoma both genetically and clinically, with adrenal tumors being associated with a more severe prognosis. The different tumor properties may be linked to specific tumor founder cells in adrenal and sympathetic ganglia. To address this question, we first set up cultures of mouse sympathetic neuroblasts and adrenal chromaffin cells.

Evaluation of Data-Driven Rigid Motion Correction in Clinical Brain PET Imaging.

Head motion during brain PET imaging can significantly degrade the quality of the reconstructed image, leading to reduced diagnostic value and inaccurate quantitation. A fully data-driven motion correction approach was recently demonstrated to produce highly accurate motion estimates (<1 mm) with high temporal resolution (≥1 Hz), which can then be used for a motion-corrected reconstruction. This can be applied retrospectively with no impact on the clinical image acquisition protocol.

The sympathies of the body: functional organization and neuronal differentiation in the peripheral sympathetic nervous system.

During the last 30 years, our understanding of the development and diversification of postganglionic sympathetic neurons has dramatically increased. In parallel, the list of target structures has been critically extended from the cardiovascular system and selected glandular structures to metabolically relevant tissues such as white and brown adipose tissue, lymphoid tissues, bone, and bone marrow. A critical question now emerges for the integration of the diverse sympathetic neuron classes into neural circuits specific for these different target tissues to achieve the homeostatic regulation of the physiological ends affected.

All-trans retinoic acid induces synaptopodin-dependent metaplasticity in mouse dentate granule cells.

Previously we showed that the vitamin A metabolite all-trans retinoic acid (atRA) induces synaptic plasticity in acute brain slices prepared from the mouse and human neocortex (Lenz et al., 2021). Depending on the brain region studied, distinct effects of atRA on excitatory and inhibitory neurotransmission have been reported.

A general principle of dendritic constancy: A neuron's size- and shape-invariant excitability.

Reducing neuronal size results in less membrane and therefore lower input conductance. Smaller neurons are thus more excitable, as seen in their responses to somatic current injections. However, the impact of a neuron's size and shape on its voltage responses to dendritic synaptic activation is much less understood.

Constitutive tumor necrosis factor (TNF)-deficiency causes a reduction in spine density in mouse dentate granule cells accompanied by homeostatic adaptations of spine head size.

The majority of excitatory synapses terminating on cortical neurons are found on dendritic spines. The geometry of spines, in particular the size of the spine head, tightly correlates with the strength of the excitatory synapse formed with the spine. Under conditions of synaptic plasticity, spine geometry may change, reflecting functional adaptations.

Functional redundancy of the premotor network in hemispherotomy patients.

Objective: Using multimodal imaging, we tested the hypothesis that patients after hemispherotomy recruit non-primary motor areas and non-pyramidal descending motor fibers to restore motor function of the impaired limb.

Methods: Functional and structural MRI data were acquired in a group of 25 patients who had undergone hemispherotomy and in a matched group of healthy controls. Patients' motor impairment was measured using the Fugl-Meyer Motor Assessment.

Maturation-Dependent Differences in the Re-innervation of the Denervated Dentate Gyrus by Sprouting Associational and Commissural Mossy Cell Axons in Organotypic Tissue Cultures of Entorhinal Cortex and Hippocampus.

Sprouting of surviving axons is one of the major reorganization mechanisms of the injured brain contributing to a partial restoration of function. Of note, sprouting is maturation as well as age-dependent and strong in juvenile brains, moderate in adult and weak in aged brains. We have established a model system of complex organotypic tissue cultures to study sprouting in the dentate gyrus following entorhinal denervation.

Prodromal sensory neuropathy in Pink1 SNCA double mutant Parkinson mice.

Aims: Parkinson's disease (PD) is frequently associated with a prodromal sensory neuropathy manifesting with sensory loss and chronic pain. We have recently shown that PD-associated sensory neuropathy in patients is associated with high levels of glucosylceramides. Here, we assessed the underlying pathology and mechanisms in Pink1 SNCA double mutant mice.

Amyloid-Beta Mediates Homeostatic Synaptic Plasticity.

The physiological role of the amyloid-precursor protein (APP) is insufficiently understood. Recent work has implicated APP in the regulation of synaptic plasticity. Substantial evidence exists for a role of APP and its secreted ectodomain APPsα in Hebbian plasticity.

Optimizing the frame duration for data-driven rigid motion estimation in brain PET imaging.

Purpose: Data-driven rigid motion estimation for PET brain imaging is usually performed using data frames sampled at low temporal resolution to reduce the overall computation time and to provide adequate signal-to-noise ratio in the frames. In recent work it has been demonstrated that list-mode reconstructions of ultrashort frames are sufficient for motion estimation and can be performed very quickly. In this work we take the approach of using image-based registration of reconstructions of very short frames for data-driven motion estimation, and optimize a number of reconstruction and registration parameters (frame duration, MLEM iterations, image pixel size, post-smoothing filter, reference image creation, and registration metric) to ensure accurate registrations while maximizing temporal resolution and minimizing total computation time.